The classic study by McCay demonstrates that dietary restriction can prolong life-span and reduce incidence of age-specific diseases. This and other similar studies suggest that nutritional manipulation could be applied to the human populations not only to increase life-expectancy, but also to avoid debilitating disease associated with old age. However, before such an application is possible, it is important to understand the theoretical principles underlying this process. I am interested in the effect of dietary restriction on the immune system during aging because of the role of the immune system in the defense against infectious diseases, malignancies, and autoimmunity. Furthermore, the decline of the immune system is demonstrated to be responsible for the increased susceptibility to these diseases. Dietary restriction not only reduces disease incidence, but it can also restore many immune functions. However, the mechanism responsible for this process is unclear. I have previously shown that lymphocyte functions decline with age as determined by their reduced proliferative capacity. Subsequent biochemical and genetic studies, found that the decline in interleukin 2 and interleukin 3 synthesis and genetic expression by helper T cells might be responsible. In this proposal, I will use the same molecular approach to elucidate the relationship between the physiological and molecular processes in T cell activation under the influence of dietary restriction. In addition, I will take a new approach in addressing the question on cellular aging by establishing cloned T cell lines from rats of different ages either with or without dietary restriction. My training in immunology, my research experience in gerontology, and my interest in dietary restriction provide me the suitable background to apply for the SERCA award.